scholarly journals Association of germline genetic variants with breast cancer-specific survival in patient subgroups defined by clinic-pathological variables related to tumor biology and type of systemic treatment

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Anna Morra ◽  
Maria Escala-Garcia ◽  
Jonathan Beesley ◽  
Renske Keeman ◽  
Sander Canisius ◽  
...  

Abstract Background Given the high heterogeneity among breast tumors, associations between common germline genetic variants and survival that may exist within specific subgroups could go undetected in an unstratified set of breast cancer patients. Methods We performed genome-wide association analyses within 15 subgroups of breast cancer patients based on prognostic factors, including hormone receptors, tumor grade, age, and type of systemic treatment. Analyses were based on 91,686 female patients of European ancestry from the Breast Cancer Association Consortium, including 7531 breast cancer-specific deaths over a median follow-up of 8.1 years. Cox regression was used to assess associations of common germline variants with 15-year and 5-year breast cancer-specific survival. We assessed the probability of these associations being true positives via the Bayesian false discovery probability (BFDP < 0.15). Results Evidence of associations with breast cancer-specific survival was observed in three patient subgroups, with variant rs5934618 in patients with grade 3 tumors (15-year-hazard ratio (HR) [95% confidence interval (CI)] 1.32 [1.20, 1.45], P = 1.4E−08, BFDP = 0.01, per G allele); variant rs4679741 in patients with ER-positive tumors treated with endocrine therapy (15-year-HR [95% CI] 1.18 [1.11, 1.26], P = 1.6E−07, BFDP = 0.09, per G allele); variants rs1106333 (15-year-HR [95% CI] 1.68 [1.39,2.03], P = 5.6E−08, BFDP = 0.12, per A allele) and rs78754389 (5-year-HR [95% CI] 1.79 [1.46,2.20], P = 1.7E−08, BFDP = 0.07, per A allele), in patients with ER-negative tumors treated with chemotherapy. Conclusions We found evidence of four loci associated with breast cancer-specific survival within three patient subgroups. There was limited evidence for the existence of associations in other patient subgroups. However, the power for many subgroups is limited due to the low number of events. Even so, our results suggest that the impact of common germline genetic variants on breast cancer-specific survival might be limited.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e12564-e12564 ◽  
Author(s):  
Ali Ayberk Besen ◽  
Huseyin Mertsoylu ◽  
Fatih Kose ◽  
Berna Yıldırım ◽  
Sedat Gozel ◽  
...  

e12564 Background: Patients with oligometastatic disease achieve long-term survival with multimodality treatment strategies. However, little attention has been paid to the effect of adjusting systemic therapy after local therapy in clinical studies. The aim of this study was to investigate the effects of changing or continuing the same treatment regimen following local therapy on survival parameters. Methods: Out of 350 metastatic breast cancer patients, treated between 2012 and 2016, 43 patients (12%) with oligometastatic disease were included in our study. Oligometastasis was defined as < 5 metastatic sites in the same or different organs. Results: At a median follow-up of 32 months (7–53 months), 29 (67.4 %) patients had died. The one- and two-year overall survival (OS) rates were 95% and 78%, respectively, and the one- and two-year progression-free survival (PFS) rates were 77% and 51%, respectively. Following stereotactic body radiotherapy (SBRT) to oligometastatic sites, systemic treatment protocols were changed in 28 (65.1%) patients, while systemic treatment was continued unchanged in 15 (34.9%) patients. Changes to systemic treatment were significantly higher in patients with two organ metastases compared to patients with one organ metastasis ( p= 0.04). In the univariate analysis, estrogen receptor (ER) status and triple negative disease were significantly predictive of OS. The ER status and the number of metastatic organs were identified as significant predictors of PFS. In the multivariate analysis, only age emerged as a significant independent predictor of OS, while the number of initial organs involved and triple negative disease were significant factors for PFS. Conclusions: A hybrid treatment strategy is associated with higher survival rates in oligometastatic breast cancer patients. Post-SBRT systemic treatment change had no significant impact on OS and PFS in this study.


2020 ◽  
Vol 50 (3) ◽  
pp. 230-240
Author(s):  
Naomi Gondo ◽  
Masataka Sawaki ◽  
Masaya Hattori ◽  
Akiyo Yoshimura ◽  
Haruru Kotani ◽  
...  

Abstract Objective The relationship between the body mass index (BMI) at the time of breast cancer diagnosis and the prognosis of breast cancer patients has not yet been clarified. We investigated the impact of obesity for clinical outcomes in Japanese breast cancer patients. Methods Women with primary breast cancer operated between 2002 and 2014 were identified. All patients are categorized into four groups according to BMI. The range of BMI is &lt;18.5 kg/m2, from 18.5 to 24.9 kg/m2, 25 to 29.9 kg/m2, &gt;30 kg/m2 in underweight, normal, overweight and obesity groups, respectively. The correlation between BMI and overall survival (OS), breast cancer-specific survival (BCSS) and disease-free survival (DFS) were statistically analyzed. Results From the database of our institution, we identified 3223 patients. The median follow-up period was 57 months (1–149). We categorized 2257 (70.0%), 318 (9.9%), 545 (16.9%) and 103 (3.2%) patients into normal, underweight, overweight obesity groups respectively. There were189 patients (5.9%) deaths due to breast cancer recurrence (137 patients) and other disease (52 patients). Obesity groups was significantly high compared with normal groups for OS (adjusted HR, 2.43; 95% CI, 1.38–4.28; P &lt; 0.001), BCSS (adjusted HR, 2.73; 95% CI, 1.15–6.44; P = 0.02) and DFS (adjusted HR, 1.83; 95% CI, 1.11–3.02; P = 0.017) by multivariate analysis. Especially, OS (adjusted HR, 4.87; 95% CI, 2.15–11.04; P &lt; 0.001), BCSS (adjusted HR, 4.51; 95% CI, 1.52–13.34; P &lt; 0.001) and DFS (adjusted HR, 4.87; 95% CI, 1.02–4.89; P = 0.04) were statistically insignificant in postmenopausal ER-positive breast cancer patients. Conclusion Obesity might be risk factor for OS, BCSS and DFS, especially postmenopausal ER-positive women.


2020 ◽  
Vol 50 (2) ◽  
pp. 104-113
Author(s):  
Jai Min Ryu ◽  
Seok Jin Nam ◽  
Seok Won Kim ◽  
Jeong Eon Lee ◽  
Byung Joo Chae ◽  
...  

Abstract Objective Demands for genetic counseling with BRCA1/2 examination have markedly increased. Accordingly, the incidence of uninformative results on BRCA1/2 mutation status has also increased. Because most patients examined for BRCA1/2 mutation have a high risk of hereditary breast and/or ovarian cancer, many patients suffer psychological distress even when the BRCA1/2 result is negative. We compared oncological outcomes between BRCA1/2-negative breast cancer with high risk of hereditary breast and/or ovarian cancer and sporadic breast cancer without risk of hereditary breast and/or ovarian cancer. Methods The criteria for high risk for hereditary breast and/or ovarian cancer were defined as family history of breast and/or ovarian cancer in first- or second-degree relative, early onset breast cancer at &lt;35 years old and bilateral breast cancer. Patients were matched maximally 1:3 into those who identified as negative for BRCA1/2 mutation with risk of hereditary breast and/or ovarian cancer (study group) and those who were not examined for BRCA1/2 mutation without risk for hereditary breast and/or ovarian cancer (control group). Matched variables were pathologic stage, estrogen receptor, progesterone receptor and human epidermal growth factor receptor-2 status. Results All matching variables were successfully matched. Median follow-up duration was 57.8 months. There was no significant difference between the groups in disease-free survival (log-rank P = 0.197); however, the study group showed significantly better overall survival and breast cancer-specific survival (both P &lt; 0.0001). We conducted subgroup analysis in the middle-aged group (36–54) and showed no significant difference for disease-free survival (P = 0.072) but significantly better overall survival and breast cancer-specific survival in the study group (P = 0.002 and P &lt; 0.0001). Conclusions BRCA1/2-negative breast cancer patients who had hereditary breast and/or ovarian cancer risk factors showed similar disease-free survival and better overall survival and breast cancer-specific survival compared with those with sporadic breast cancer without hereditary breast and/or ovarian cancer risk factors.


2021 ◽  
Vol 18 (1) ◽  
pp. 1-14
Author(s):  
Paulo Luz ◽  
Elsa Campoa ◽  
Rita Gameiro ◽  
Marta Vaz ◽  
Isabel Fernandes ◽  
...  

Over the last years, the incidence of brain metastases in HER2 breast cancer patients has increased. Surgery and radiotherapy are the current standard local therapies. Nevertheless, it is unclear which and when systemic treatment should be applied in addition to local treatment. This work aims to present an updated review of current systemic treatment options for patients with HER2+ metastatic breast cancer with brain metastases and to present a case study of clinical cases that occurred in a Portuguese population. The methodology of this work included a literature search in PubMed for the impact of HER2-targeting agents, such as pertuzumab, trastuzumab emtansine (T-DM1), lapatinib, neratinib, trastuzumab deruxtecan, and tucatinib in the treatment of patients with HER2+ breast cancer with brain metastases. Then, a cohort of Portuguese patients with HER2+ breast cancer (n=44) was analyzed. In this exploratory study, considering a follow-up of 23.9 months, three patients (6.8%) developed brain metastases despite having shown a complete pathological response. The role of systemic treatment for patients with HER2 breast cancer with brain metastases has rapidly evolved following recent successes in phase II and III clinical trials. The biggest challenge is how to integrate systemic and local treatment in the management of these patients.


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